Renal Vacuolar H<sup>+</sup>-ATPase

Wagner, Carsten A.; Finberg, Karin E.; Breton, Sylvie; Marshansky, Vladimir; Brown, Dennis; Geibel, John P.

doi:10.1152/physrev.00045.2003

Cited by 411 publications

(501 citation statements)

References 554 publications

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“…Zebrafish HR cells specifically express apical H + -ATPase and NHE as do mammalian renal proximal tubular cells (Yan et al, 2007), which are responsible for about 70% of sodium and 80% of bicarbonate reabsorption in mammalian nephrons (Wagner et al, 2004). As HR cells were demonstrated to have similar functions of acid-base regulation and Na + uptake, they should also express carbonic anhydrases (CAs) and the basolateral H + -HCO 3 + cotransporter (NBC) to fulfill the transepithelial transport mechanisms, as do proximal tubular cells.…”

Section: Membrane-associated and Cytosolic Carbonic Anhydrasesmentioning

confidence: 99%

Ion uptake and acid secretion in zebrafish (Danio rerio)

Hwang

2009

Journal of Experimental Biology

166

165

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SummaryTransepithelial transport is one of the major processes involved in the mechanism of homeostasis of body fluids in vertebrates including fish. The current models of ion regulation in fish gill ionocytes have been proposed mainly based on studies in traditional model species like salmon, trout, tilapia, eel and killifish, but the mechanisms are still being debated due to the lack of convincing molecular physiological evidence. Taking advantage of plentiful genetic databases for zebrafish, we studied the molecular/cellular mechanisms of ion regulation in fish skin/gills. In our recently proposed model, there are at least three subtypes of ionocytes in zebrafish skin/gills: Na + -K + -ATPase-rich (NaR), Na + -Cl -cotransporter (NCC) and H + -ATPase-rich (HR) cells. Specific isoforms of transporters and enzymes have been identified as being expressed by these ionocytes: zECaC, zPMCA2 and zNCX1b by NaR cells; zNCC gill form by NCC cells; and zH + -ATPase, zNHE3b, zCA2-like a and zCA15a by HR cells. Serial molecular physiological experiments demonstrated the distinct roles of these ionocytes in the transport of various ions: HR, NaR and NCC cells are respectively responsible for acid secretion/Na + uptake, Ca 2+ uptake and Cl -uptake. The expression, regulation and function of transporters in HR and NaR cells are much better understood than those in NCC cells. The basolateral transport pathways in HR and NCC cells are still unclear, and the driving forces for the operations of apical NHE and NCC are another unresolved issue. Studies on zebrafish skin/gill ionocytes are providing new insights into fish ion-regulatory mechanisms, but the zebrafish model cannot simply be applied to other species because of species differences and a lack of sufficient molecular physiological evidence in other species.

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Section: Membrane-associated and Cytosolic Carbonic Anhydrasesmentioning

confidence: 99%

Ion uptake and acid secretion in zebrafish (Danio rerio)

Hwang

2009

Journal of Experimental Biology

166

165

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“…V-type H + -ATPases are multi-subunit protein complex consisting of at least 14 subunits in humans (for a detailed review on H + -ATPase structure, function, and regulation, see recent reviews: (54,55,119,122,202)). Most subunits occur in different isoforms that may be specific to organs, cell types, or subcellular organelles.…”

Section: The Major Transport Proteins H-atpasesmentioning

confidence: 99%

Regulated acid–base transport in the collecting duct

Wagner

Devuyst

Bourgeois

et al. 2009

Pflugers Arch - Eur J Physiol

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161

142

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The renal collecting system serves the fine-tuning of renal acid-base secretion. Acid-secretory type-A intercalated cells secrete protons via a luminally expressed V-type H(+)-ATPase and generate new bicarbonate released by basolateral chloride/bicarbonate exchangers including the AE1 anion exchanger. Efficient proton secretion depends both on the presence of titratable acids (mainly phosphate) and the concomitant secretion of ammonia being titrated to ammonium. Collecting duct ammonium excretion requires the Rhesus protein RhCG as indicated by recent KO studies. Urinary acid secretion by type-A intercalated cells is strongly regulated by various factors among them acid-base status, angiotensin II and aldosterone, and the Calcium-sensing receptor. Moreover, urinary acidification by H(+)-ATPases is modulated indirectly by the activity of the epithelial sodium channel ENaC. Bicarbonate secretion is achieved by non-type-A intercalated cells characterized by the luminal expression of the chloride/bicarbonate exchanger pendrin. Pendrin activity is driven by H(+)-ATPases and may serve both bicarbonate excretion and chloride reabsorption. The activity and expression of pendrin is regulated by different factors including acid-base status, chloride delivery, and angiotensin II and may play a role in NaCl retention and blood pressure regulation. Finally, the relative abundance of type-A and non-type-A intercalated cells may be tightly regulated. Dysregulation of intercalated cell function or abundance causes various syndromes of distal renal tubular acidosis underlining the importance of these processes for acid-base homeostasis.

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“…The v-H + -ATPase and its associated protein, (P)RR, are predominantly expressed at the apical surface of the collecting duct where it functions to expel protons into the tubular lumen, thereby contributing to urinary acidification. 126 The findings that the collecting duct is a key site of local RAS activity, where renin is produced in abundance by collecting duct principal cells 127 suggest an Ang-IIdependent activation of the collecting duct v-H + -ATPase and modulation of urinary acidification. 128,129 In agreement with these results, Advani et al 113 concluded that the (P)RR has a primary role in distal nephron proton transport, which at least in part, an Ang-II-dependent phenomenon.…”

Section: The Cross-talk: (P)rrs and Wnt/fz Signaling Systemmentioning

confidence: 99%

Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

Balakumar

Jagadeesh

2011

Hypertens Res

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The renin-angiotensin system and Wnt/frizzled receptor signaling pathways are important in the development of essential organs, and their aberrant activation results in cardiovascular and renal pathologies. The (pro)renin receptor ((P)RR)-bound (pro)renin is enzymatically active generating angiotensin-II and activating mitogen-activated protein kinases, leading to cell proliferation and to upregulation of profibrotic genes expression, resulting in end-organ damage. The (P)RR does more than bind to (pro)renin, because it is functionally linked to the vacuolar-H + -ATPase (v-H + -ATPase) that regulates pH of cellular and intracellular vesicles, and to Wnt signaling. This signaling pathway is essential for cell survival, embryonic development and has had a role in various disease states as evidenced by mutation or genetic ablation of the (P)RR gene. This suggests two types of functions of (P)RRs, first one as a receptor for (pro)renin and second one as an accessory subunit of the v-H + -ATPase and a cofactor of the Wnt/Fz receptor complex. This review will discuss both of these functions of (P)RRs thereby giving new perspectives as to the roles of (P)RRs in cardiovascular and renal pathologies.

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Renal Vacuolar H⁺-ATPase

Cited by 411 publications

References 554 publications

Ion uptake and acid secretion in zebrafish (Danio rerio)

Ion uptake and acid secretion in zebrafish (Danio rerio)

Regulated acid–base transport in the collecting duct

Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

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Renal Vacuolar H+-ATPase

Cited by 411 publications

References 554 publications

Ion uptake and acid secretion in zebrafish (Danio rerio)

Ion uptake and acid secretion in zebrafish (Danio rerio)

Regulated acid–base transport in the collecting duct

Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

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Resources

About

Renal Vacuolar H⁺-ATPase